Morphology and serum and bone tissue calcium and magnesium concentrations in the bones of male rats chronically treated with letrozole, a nonsteroidal cytochrome P450 aromatase inhibitor

Connect Tissue Res. 2021 Jul;62(4):454-463. doi: 10.1080/03008207.2020.1771329. Epub 2020 May 27.

Abstract

Purpose/Aim of the study: The role of estrogen (E) in the regulation of bone turnover in women is well established, though the contributions of E versus testosterone (T) in the control of bone turnover in men are poorly understood. The aim of this study was to examine the association between chronic treatment with letrozole, a nonsteroidal inhibitor blocking the aromatase activity and thus the conversion of androgens into estrogens, and cortical bone morphology in the femur and humerus of male adult rats.Materials and Methods: Adult male rats were treated with letrozole for 6 months and the body and femur weight, morphology, collagen structure, blood serum, and bone tissue concentrations of calcium and magnesium were examined.Results: Long-term aromatase inhibition resulted in a decrease in femur mass, a wavelike arrangement of bone and lamellae with an altered organization of collagen in compact bone, a increased concentration of calcium in blood serum, and no change in calcium bone tissue concentration, magnesium serum, or bone tissue concentration. MicroCT study of the humerus revealed significant decreases of whole bone tissue volume, cortical bone thickness, cortical bone volume, and external cortical bone thickness with letrozole treatment.Conclusion: Chronic treatment with letrozole affected cortical bone structure and produced histomorphological changes in male rat bone similar to that observed in the aging processes.

Keywords: Bone μCT; bone loss; estrogen; letrozole; male.

MeSH terms

  • Animals
  • Aromatase
  • Aromatase Inhibitors* / pharmacology
  • Bone and Bones
  • Calcium*
  • Collagen
  • Estradiol
  • Estrogens
  • Letrozole
  • Magnesium
  • Male
  • Nitriles / pharmacology
  • Rats
  • Serum
  • Triazoles / pharmacology

Substances

  • Aromatase Inhibitors
  • Estrogens
  • Nitriles
  • Triazoles
  • Estradiol
  • Letrozole
  • Collagen
  • Aromatase
  • Magnesium
  • Calcium